Human diseases caused by hepatitis B virus and human T lymphotropic virus-type III (HTLV-III) have had worldwide impact and are the focus of intense current investigation. Viremia can persist with both viruses but can be blocked or reversed in the case of hepatitis B by anti-HBsAG antibody. Human anti-HBsAg is currently available only from serum of previously infected individuals and is in limited supply, whereas a consistent source of neutralizing antibodies against HTLV-III has yet to be identified. Human monoclonal antibodies against these two viruses would more precisely delineate antigen determinants which elicit humoral responses, allow for the investigation of the viral-neutralizing potency of various antibodies, and provide a means of obtaining large quantities of specific antibody for therapeutic studies. Immediate applications of viral-specific IgM monoclonal antibodies would be to perfect and define existing serological asays. Antigen-specific B cells from peripheral blood or enlarged lymph nodes will be immortalized with either Epstein-Barr virus (EBV) or HTLV-I, cloned by limiting dilution immediately after infection, and recloned rapidly at 3 to 4 weeks. Activated normal antigen-specific B cells or selected antigen-specific EBV lines will be fused with appropriate partners and antigen-specific B-B hybridomas will be constructed to obtain a more stable source of antibody in higher concentrations. Results from these studies should more precisely delineate the kinetics of the appearance of certain subsets of antigen-specific IgM or IgG producing B cells in defined lymphoid compartments. Antibodies produced by these specific lines will be purified, characterized as to isotype and subclass, and studied for binding to related antigens. Anti-HBsAG antibodies will be used to define the determinants against which they are directed and IgM isotypes will be utilized to perfect anti-HBsAG assays to eliminate spurious positive results. Anti-HTLV-III monoclonals will be investigated for their capacity to block HTLV-III infection of susceptible cells. If blocking antibodies are uncovered, the precise epitopes on the HTLV-III envelope against which they are directed will be defined. IgM anti-HTLV-III will also be used to explore whether some "seronegative" individuals have serum IgM specific for virus and indicative of early HTLV-III infection. This would allow the detection of contagious blood which might not be detected by current assays. The study of monoclonal human anti-HTLV-III antibodies should provide new insights into the nature of HTLV-III infection and the immune response against it.